In stent restenosis in interventional catdiology

All about in stent restenosis

1. Contents Introduction (what is ISR , definitions, classification) Mechanisms of ISR Imaging for ISR Management principles Adjunctive therapeutic modalities for ISR Summary

2. Introduction In-stent restenosis (ISR) is characterized by a significant reduction in the luminal diameter within the stented segment after a successful percutaneous coronary intervention (PCI). accounts for 5-10% of all PCI procedures performed in clinical practice. DEFINITION: A reduction ≥50% of the luminal diameter within the previously stented segment or the vessel segments 5 mm proximal and distal to the stent (the “stent edges”), as assessed by coronary angiography. (Kuntz RE, Baim DS. Defining coronary restenosis. Newer clinical and angiographic paradigms. Circulation. 1993 Sep;88(3):1310–23.)

3. Using intravascular imaging (IVI), which acquires data in three dimensions, ISR has been defined as a re-narrowing of ≥75% of the reference vessel area in cross-section. Angiographic classification: - The most used ISR classification system was proposed by Mehran et al (1999) - This system classified patients with BMS-ISR into groups based on three characteristics: ISR length (≤10 mm: focal, >10 mm: diffuse), ISR location (within or beyond stent borders), and occlusion (yes or no) - Type I: focal Type II: diffuse, within stent; Type III: diffuse, within and beyond stent Type IV: occlusive

4. Mechanisms of ISR Mechanical / technical factors Biological mechanisms

5. Imaging for ISR Expert consensus and guidelines recommend (Class IIa , Level B) the use of IVI in order to assess ISR. 1 ) OCT: optical coherence tomography - wavelength of 1.3 μm and axial resolution of 12-15 μ m Based on OCT appearances, ISR can be classified into four groups : – Homogeneous: uniform high signal intensity, low back-scatter, typical of areas of high smooth muscle cell content – Heterogeneous: mixed signal intensity, may represent the presence of proteoglycan-rich neointimal or early neo-atherosclerotic plaque – Attenuated: superficial high signal intensity, high back-scatter, likely indicative of lipid-core plaque – Layered: most frequently presenting as superficial high signal intensity with a deep low signal intensity often in peri-strut areas

6. 2) IVUS: Intravascular ultrasound IVUS results in deeper tissue penetration, in comparison to OCT, and a blood-free field is not required. wavelength of IVUS is ~50 μm with an axial resolution of 150 μm ,

7. Management principles Acute gain is defined as the difference between the MLD pre-procedure and the MLD immediately post-procedure. LLL is defined as the difference between the MLD immediately post-procedure and the MLD at follow-up angiography

8. A variety of treatment modalities have been compared directly in head-to-head studies and indirectly in network meta-analyses. When all of these treatment strategies have been compared using network meta-analysis, two modalities have consistently emerged as pre-eminent for the management of ISR: DES implantation and treatment with DCBs

9. Drug-eluting stents DESs are recognized for their strong anti-proliferative properties and are therefore a good choice for the management of ISR Network meta-analyses have ranked DES implantation as the most effective treatment for ISR. In addition, head-to-head trials have demonstrated the superiority of DES implantation to several other therapeutic modalities for ISR, including BA, intravascular brachytherapy (IVBT), and paclitaxel DCB

10. DES STRATEGY: HETERO-DES VS HOMO-DES treating DES-ISR using a DES with an alternative anti-proliferative agent (the “hetero-DES” strategy) might provide superior outcomes to using a DES with the same antiproliferative agent (the “homo-DES” strategy). evidence in this regard has been mixed ISAR DESIRE-2 (2010), did not show a benefit to the hetero-DES strategy for the treatment of sirolimus-eluting stent ISR , RIBS-III study had suggested a hetero-DES strategy may provide superior outcomes.

11. Drug coated balloons (DCBs) DCB catheters are comprised of standard angioplasty balloons and a matrix coating that is applied to the surface of the balloon. The balloon coating is typically comprised of two elements: a lipophilic active drug and a spacer or excipient which increases the solubility of the active drug and facilitates its transfer from the balloon surface to the vessel wall. Paclitaxel DCB Sirolimus DCB, - limus-elutingDCB

12. Adjunctive therapeutic modalities for ISR BALLOON ANGIOPLASTY- BA was the earliest treatment available for ISR but was subsequently shown to be inferior to multiple newer alternative treatment m odalities CUTTING/SCORING BALLOONS – Cutting balloons are comprised of standard balloon catheters mounted with lateral metallic blades, which on inflation of the balloon incise into the treated stenotic plaque. Scoring balloons have a broadly similar mechanistic basis but employ low-profile nitinol wires (of the order of 125 μm ) on the surface of the balloon catheter in a spiral formation.

13. INTRAVASCULAR BRACHYTHERAPY D elivery of localized radiation within the stent The radiation achieves this effect via two primary methods: direct damage secondary to ionizing emissions and injury secondary to free radical generation. ROTATIONAL ATHERECTOMY INTRAVASCULAR LITHOTRIPSY a relatively new technology that uses localized pulsatile sound waves to circumferentially modify vascular calcium

14. ISR treatment algorithm